KCNB1 gene polymorphisms and related indel as predictor biomarkers of treatment response for colorectal cancer – toward a personalized medicine

Abstract

The KCNB1 gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the KCNB1 gene variants rs3331, rs1051295, and indel (insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 ± 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy based on fluorouracil. KCNB1 genotyping was performed with amplification-refractory mutation system–polymerase chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness. Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement ( p adjusted < 0.001). Stratification of colorectal cancer patients’ response according to tumor localization and TNM stages reveals negative association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcino-embryonic antigen ( p = 0.043) and CA19-9 ( p = 0.014) serum levels. On the other hand, the presence of rs1051295 (homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. KCNB1 haplotype did not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific strategies for screening treatment and prevention protocols as well as KCNB1 variants may constitute an effective model for ongoing personalization medicine.

A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database

“…OR10Q1 encodes for an olfactory receptor that has so far not been studied [ 117 ]. KCNB1 is a potassium voltage-gated channel that is highly expressed in the brain and has been identified as a biomarker for colorectal cancer and associated with a favorable prognosis in glioma patients [ 114 , 118 , 119 ]. Specifically, it was shown that KCNB1 regulates autophagy through the ERK signaling pathway and acts as a tumor suppressor [ 114 ].…”

Altered expression of cytokines, chemokines, growth factors, and soluble receptors in patients with colorectal cancer, and correlation with treatment outcome

“…The elevation in serum levels of the identified mediators in patients with CRC patients underscores the state of inflammation accompanying CRC [ 18 , 19 ]. It was shown that heightened IFN-γ levels are generally tumor-suppressive [ 8 , 19 ], and that deficiency of IFN-γ or its receptor-promoted colorectal carcinogenesis [ 20 ], thus prompting the conclusion of a key role for IFN-γ in patient survival [ 3 , 21 ].…”

Western influenced lifestyle and Kv2.1 association as predicted biomarkers for Tunisian colorectal cancer

“…The surprising variability of Kv2.1 function within the microenvironment highlights the possible if not likely importance of such channels in CRC and suggests additional studies to discover Kv2.1 function that may be modified adversely with Western influenced lifestyles such as increased fat and meat consumption. In addition, our recent results showed that KCNB1 polymorphisms were associated with Tumor-Node-Metastasis (TNM) progression and treatment response and suggests that such polymorphisms as biomarkers of CRC outcomes, before and during chemotherapy process [ 17 ]. The accumulated body of evidence of the importance and functional contribution of Kv2.1 in cancer suggested the importance of testing variants’ of KCNB1 (the Kv2.1 coding gene) association with CRC, CC and RC.…”

“…Consideration of such protein families’ role in apoptosis regulation suggests that potassium channels are regulators of cancer cell death and may lead to promising therapeutic targets. In particular, a recent study by this group provides evidence about the association of KCNB1 polymorphisms (rs3331, rs1051295 and rs11468831) and treatment response and may help predict if not contribute to anticancer treatment response, a part of a new approach for monitoring the disease kinetics during the chemotherapy process [ 17 ].…”